A5038183050- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Thyroid Cancer Diagnosis and Treatment
- Estrogen and related hormone effects
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- Neonatal Health and Biochemistry
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Mechanisms of cancer metastasis
- Cancer Mechanisms and Therapy
- Neuroscience of respiration and sleep
- Pituitary Gland Disorders and Treatments
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Blood groups and transfusion
- Congenital heart defects research
- Hormonal and reproductive studies
- Sexual Differentiation and Disorders
- Hypothalamic control of reproductive hormones
- Cancer, Hypoxia, and Metabolism
- Birth, Development, and Health
- Circadian rhythm and melatonin
- RNA and protein synthesis mechanisms
- Hormonal Regulation and Hypertension
University of Chicago
2015-2024
Monash University
2020-2021
University of Illinois Chicago
1977-2021
Pediatrics and Genetics
2007-2019
Memorial Sloan Kettering Cancer Center
2014
Royal Devon & Exeter NHS Foundation Trust
2012
University of Chicago Medical Center
1995-2011
Aarhus University
2010
Immunovaccine (Canada)
2005-2009
Penteli General Children's Hospital
2007
The occurrence of a bizarre familial syndrome combining deaf-mutism, stippled epiphyses, goiter and abnormally high PBI in 2 6 children consanguineous marriage is described. Mean levels were 14 21 μg/100 ml; BEI 9 15 T4-by-column 11 24-hr 131I uptake 49 70%; PB13lI conversion ratios 40 41%; thyro-binding index 0.81 0.93; TBG 17 20 antithyroglobulin titer less than 1:16. Potassium perchlorate discharge test was normal. Iodine metabolism studied one subject revealed thyroid iodine clearance 24...
To define the roles of circadian rhythmicity (intrinsic effects time day independent sleep or wake condition) and condition, irrespective day) on 24-h variation in glucose tolerance, eight normal men were studied during constant infusion for a total 53 h. The period study included 8 h nocturnal sleep, 28 continuous wakefulness, daytime sleep. Blood samples measurement glucose, insulin, C-peptide, cortisol, growth hormone collected at 20-min intervals throughout entire study. Insulin...
Abstract The BRAFT1799A mutation is the most common genetic alteration in papillary thyroid carcinomas (PTC). It also found a subset of microcarcinomas, consistent with role tumor initiation. PTCs are often invasive and present at more advanced stage. high prevalence tall-cell variant poorly differentiated undifferentiated arising from PTCs. To explore BRAFV600E cancer pathogenesis, we targeted its expression to cells transgenic FVB/N mice bovine thyroglobulin promoter. Two Tg-BRAFV600E...
Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree which these cancers dependent on expression is still unclear. To address this question, we generated mice expressing one most commonly detected mutations in papillary carcinomas (BRAF(V600E)) follicular cells doxycycline-inducible (dox-inducible) manner. Upon dox induction...
Hormone-resistance syndromes can be broadly defined as conditions resulting from reduced or absent end-organ responsiveness to biologically active hormones. They are caused by defects in hormone receptors post-receptor defects.1–3 Mutations the thyroid hormone–receptor β gene cause resistance hormone, which is characterized elevated serum concentrations with few no clinical and biochemical manifestations of excess and, most notably, normal slightly increased thyrotropin secretion.1 that...
Dual oxidase 2 (DUOX2), an NADPH:O2 oxidoreductase flavoprotein, is a component of the thyroid H2O2 generator crucial for hormone synthesis at apical membrane. Mutations in DUOX2 produce congenital hypothyroidism humans. However, no functional DUOX-based NADPH has ever been reconstituted plasma membrane transfected cells. It proposed that DUOX retention endoplasmatic reticulum (ER) heterologous systems due to lack unidentified required maturation enzyme. By data mining massively parallel...
Hyperestrogenemic states, including pregnancy, cause an increase in serum T4-binding globulin (TBG) concentrations and the proportion of TBG molecules with greater anodal mobility on isoelectric focusing, indicating sialic acid content. The possible causal relationship between degree sialylation accumulation was explored by measuring vivo half-lives (t½) TBGs different points. unfractionated its major peaks, isolated chromatofocusing defined their points focusing were each injected iv into...
Mutations of the X-linked thyroid hormone (TH) transporter (monocarboxylate transporter, MCT8) produce in humans unusual abnormalities function characterized by high serum T3 and low T4 rT3. The mechanism these changes remains obscure raises questions regarding regulation intracellular availability metabolism TH. To study pathophysiology MCT8 deficiency, we generated Mct8 knockout mice. Male mice deficient (Mct8(-/y)) replicate observed affected men. TH deprivation replacement with L-T3...
Patients with mutations in the thyroid hormone receptor beta (TRbeta) gene manifest resistance to (RTH), resulting a constellation of variable phenotypic abnormalities. To understand molecular basis underlying action mutant TRbeta vivo, we generated mice targeted mutation (TRbetaPV; PV, kindred PV) by using homologous recombination and Cre/loxP system. Mice expressing single PV allele showed typical abnormalities function found heterozygous humans RTH. Homozygous exhibit severe dysfunction...
The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels in the presence an overall eumetabolic state and failure respond normally triiodothyronine. We have evaluated a family with inherited for abnormalities nuclear receptors. A single guanine----cytosine replacement codon amino acid 340 resulted glycine----arginine substitution hormone-binding domain one two alleles patient's receptor beta gene. In vitro translation products this mutant...
AbstractThyroid hormone receptors are encoded by the TRα(NR1A1) and TRβ (NR1A2) loci. These genes transcribed into multiple variants whose functions unclear. Analysis gene inactivation in mice has provided new insights functional complexity of these products. Different strategies designed to modify TRα locus have led strikingly different phenotypes. In order analyze molecular basis for alterations, we generated devoid all known isoforms produced from (TRα0/0). viable exhibit reduced linear...
We have demonstrated that T3 increases the expression of ZAKI-4alpha, an endogenous calcineurin inhibitor. In this study we characterized a T3-dependent signaling cascade leading to ZAKI-4alpha in human skin fibroblasts. found increase was greatly attenuated by rapamycin, specific inhibitor protein kinase, mammalian target rapamycin (mTOR), suggesting requirement mTOR activation T3. Indeed, activated rapidly through S2448 phosphorylation, phosphorylation p70(S6K), substrate mTOR. This is...
Thyroid function was evaluated in 46 patients with end-stage kidney disease and 42 normal subjects. Patients were studied before after the institution of maintenance hemodialysis (HD) renal transplantation (RT). Serum total triiodothyronine concentrations (TT3, ng/100 ml, mean±SD) 63±17 83±22 non-HD HD groups, respectively. Values from subjects 128±25 RT 134±20. The TT3 hypothyroid range (<78 ml; 2 SD below mean) 80% 43% patients. Mean serum thyroxine concentration (TT4), although within...